Medical device for preservation of a corneal tissue, comprising an applanation lid, and optionally a trepanation lid

ABSTRACT

The invention relates to a medical device for preservation of corneal tissue ( 3 ) that has been obtained beforehand by sampling, the device comprising a base ( 11 ), at least one side wall ( 12 ), and means for receiving and blocking the corneal tissue ( 3 ), characterized in that the device additionally comprises an applanation lid ( 13 ) for covering an opening of the device opposite the transparent base ( 11 ), the applanation lid ( 13 ) comprising: a transparent window ( 131 ), and a support ( 132 ) between the window ( 131 ) and the side wall ( 12 ), the support ( 132 ) comprising means for moving the window ( 131 ) in translation with respect to the side wall ( 12 ) of the device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national phase filing under 35 U.S.C. § 371 ofInternational Application No. PCT/EP2018/084916 filed on Dec. 14, 2018,which claims benefit of priority from French Patent Application No.1762208 filed Dec. 15, 2017, the contents of which are herebyincorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to the general technical field of medicaldevices for preservation and/or quality control (imaging,microbiological analysis, etc.) and/or treatment of human or animalcorneal tissue previously removed from a donor. This corneal tissue iscomposed of the cornea and a peripheral scleral ciliary zone surroundingthe cornea.

Such preserved corneal tissue can be used to perform cornealtransplantation, or for ex vivo experimentation.

More precisely, the present invention relates to the technical field ofdevices for preserving corneal tissue comprising:

-   -   means for receiving and locking corneal tissue,    -   means for circulating one (or more) fluid(s) (liquid or gaseous)        for preserving corneal tissue.

BACKGROUND OF THE INVENTION

Various devices for preserving corneal tissue have already beenproposed.

Document U.S. Pat. No. 5,789,240 describes a device for preservingcorneal tissue simulating the anterior chamber of the eye. This devicedoes not permit sterile circulation of a preserving fluid on both sidesof the corneal tissue, i.e., on both the epithelial and endothelialsides of the corneal tissue. In addition, because the walls of thedevice are not transparent, it is not possible to perform corneal tissueimaging or a laser cutting procedure without opening the device. As aresult, the survival time of the corneal tissue is short andincompatible with use for corneal transplantation.

Document WO 2014/140434 describes a corneal tissue preservation deviceto address these drawbacks.

The device according to WO 2014/140434 includes:

-   -   means for receiving a corneal specimen including a first        part—called the “intermediate component”—comprising a hole of        the diameter of the cornea surrounded by a circular groove and        an edge forming a housing intended to receive the corneal        specimen, the housing ensuring the correct centering of the        corneal specimen when it is placed in the device and allowing        the corneal specimen to remain stable when the device is opened        in the operating theatre;    -   means of confinement comprising a second part—called the        “endothelial lid”—comprising a hole the diameter of the cornea        surrounded by an edge intended to entrap the corneal specimen by        crushing a scleral ciliary zone of the corneal specimen onto the        circular groove of the intermediate component,        the means for receiving and entrapping the corneal specimen        sealingly locking the scleral ciliary zone surrounding the        cornea to delimit a separate endothelial chamber and epithelial        chamber in which a preservation medium can circulate with an        overpressure in the endothelial chamber.

The preservation device described in WO 2014/140434 has many advantagesand allows long-term preservation of corneal tissue.

The present invention is intended to improve the device described in WO2014/140434.

In particular, a purpose of the present invention is to provide astorage device in which:

-   -   the corneal tissue can be stored for a longer period,    -   the quality of corneal tissue and its imaging are improved,    -   the handling of the corneal tissue contained in the device is        facilitated (in particular with regard to the lamellar or        vertical cutting of the corneal tissue in a closed vessel by        laser at the corneal bank or in the operating theatre (thanks to        an applanation cover which will be described hereinbelow), its        mechanical vertical trepanation in the operating theatre (thanks        to a trepanation cover which will also be described        hereinbelow), etc.

BRIEF DESCRIPTION OF THE INVENTION

For this purpose, the invention provides a medical device forpreservation of previously removed corneal tissue, the device comprisingan at least partially transparent base, at least one side wall, meansfor receiving and locking corneal tissue, and an applanation lid forcovering an opening opposite the base, the applanation lid including atransparent window, remarkable in that the applanation lid furtherincludes a support between the window and the side wall, the supportcomprising means for translatory displacement of the window relative tothe side wall of the device.

Preferred but non-limiting aspects of the medical device according tothe invention are the following:

-   -   the support can be made of an elastically deformable soft        material;    -   the device is configured such that, in use, the receiving and        locking means define, together with the base, the corneal        tissue, the side wall and the lid, an endothelial chamber and an        epithelial chamber, the endothelial and epithelial chambers        including inlet and outlet ports for the circulation of a gas        and/or a preserving fluid, the support which may include a        release zone for receiving part of the gas and/or preserving        fluid contained in the epithelial chamber when the window is        moved translationally towards the base;    -   the means for translational movement may comprise an annular        bellows having at least one pleat;    -   the annular bellows can be made of a shape-reversing material;    -   the side wall comprises an annular rib; this annular rib is        intended to cooperate with means for fastening the lid (such as        fastening hooks) to allow the removable fastening of the lid to        the side wall,    -   the device may further comprise a trepanation lid including a        circular outer casing, a blade holder, and a cylindrical blade,        the applanation lid being replaceable with the trepanation lid        to cover an opening opposite the base (11); in which case the        medical device is a kit including both the applanation lid and        the trepanation lid, the trepanation lid being mountable on the        side wall in place of the applanation lid, for example to        perform corneal tissue cutting in the operating theatre,    -   the outer casing of the trepanation lid may have at least two        fastening hooks at its periphery, the fastening hooks extending        radially and being intended to cooperate with the rib provided        in the outer face of the side wall; this facilitates the        installation of the trepanation lid,    -   the side wall may comprise a peripheral flange, and the base may        comprise clipping means, said clipping means consisting of at        least two elastic tabs for cooperation with the peripheral        flange;    -   the clipping means may comprise at least three elastic tabs        uniformly distributed around the side wall.

BRIEF DESCRIPTION OF THE DRAWINGS

Other advantages and features of the device according to the inventionwill become clearer from the description that will follow of severalalternative embodiments, given by way of non-limiting examples, from theappended drawings wherein:

FIG. 1 is a schematic representation of corneal tissue preservationchambers (endothelial chamber and epithelial chamber),

FIGS. 2, 3 and 4 are schematic representations of a cartridgeincorporating the corneal tissue preservation chambers and all thenecessary peripherals (channels, reservoir, recovery compartment,gas-controlled valves, channels and propellant connection tip),

FIG. 5 is a schematic representation of a docking station adapted toreceive a plurality of cartridges as shown in FIGS. 2 to 4,

FIGS. 6 and 7 are functional representations of two alternativeembodiments of cartridges,

FIG. 8 is a schematic representation of a cartridge switching system,

FIGS. 9 and 10 are schematic representations of a medical deviceapplanation lid,

FIGS. 11 and 12 are partial schematic representations of the medicaldevice. These figures illustrate the principle of operation of theapplanation lid shown in FIGS. 9 and 10,

FIGS. 13 and 14 are schematic representations showing a trepanation lidof the medical device.

DETAILED DESCRIPTION OF THE INVENTION

Various examples of the medical device will now be described withreference to the figures. In these different figures the equivalentelements are designated by the same numerical reference.

1. General Information about the Device

1.1. General Structure of the System

With reference to FIG. 1, preservation chambers 1 of the device, inparticular endothelial and epithelial chambers, have been illustrated,these preservation chambers 1 being delimited by:

-   -   previously removed corneal tissue on the one hand, and    -   a base 11, at least one side wall 12 and a lid C of the device        on the other hand.

The base 11 is preferably made of a material transparent to lightradiation, either in its entirety or in an area opposite the lid C.

The lid C can consist of:

-   -   a “standard” lid (including a covering wall to cover an upper        opening in the side wall 12 opposite the base, and peripheral        fastening means) this standard lid has at least one transparent        part facing the corneal tissue, or    -   an applanation lid 13 for example for laser cutting or imaging        corneal tissue, or    -   a trepanation lid 15 for mechanical trepanation of corneal        tissue, or    -   any other type of lid depending on the intended application.

In the embodiment illustrated in FIG. 1, the preservation chambers 1have a cylindrical shape. However, the preservation chamber 1 may haveother shapes (for example parallelepiped, ovoid, etc.) depending on theintended application.

The base 11, the side wall 12 and the lid C can be made in two or morepieces.

For example, in a first embodiment, the base 11 and the side wall 12 aremade in one piece. In this case the base 11 is transparent to allowinspection of the corneal specimen (visual as well as by any optical orultrasonic means), while the lid C consists of an independent partintended to close the upper opening. The lid C also has at least onetransparent central part to allow inspection of the corneal specimenvisual as well as by any optical or ultrasonic means).

In a second embodiment, the lid C and the side wall 12 are made in onepiece.

Finally, in a third embodiment, and as shown in the alternativeembodiments illustrated in FIGS. 9-10 and 13-14, the base 11, the sidewall 12 and the lid can consist of three independent parts for assembly.In these different alternatives, the base 11 includes clipping means 111intended to cooperate with a peripheral flange 122 extending radiallyoutwards from the side wall 12.

The clipping means 111 may comprise two (or more) spring-back elastic(for example shape memory) tabs arranged opposite each other andextending substantially perpendicular to the base 11. When the base 11comprises more than two elastic tabs, these may be uniformly distributedat different positions of the base 11 so as to surround the side wall12. The fact that the elastic tabs are uniformly distributed makes itpossible to apply a substantially homogeneous force over the entireperiphery of the side wall 12.

Each elastic tab is provided with a hooking lip at its free end. Eachhooking lip projects in a horizontal plane (parallel to the base 11). Ofcourse, clip elements 111 could be of any other type known to theskilled person.

Advantageously, each elastic tab can include a zone of weakness allowingthe elastic tab to break when a force (above a threshold value) isapplied in a direction opposite to the hooking lip. This makes it easierto release the side wall 12 in order to free the corneal tissue during acorneal graft surgery procedure, for example.

It is quite obvious to the skilled person that in certain embodiments,the elastic tabs can be devoid of zones of weakness. Therefore, in theseembodiments, the elastic tabs can be moved apart (without breaking) toallow the removal and replacement of the lid C at the time ofcollection, for example when the centering of the cornea has not beencarried out correctly.

1.2. Device Integration

The medical device may consist of a cartridge with the preservationchambers 1 for receiving the corneal tissue 3.

The cartridge 2 can be parallelepiped and include:

-   -   one (or more) input connection terminal(s) 21 opening to the        outside of the cartridge 2, and intended to be connected to        means for linking a docking station 6 (which will be described        hereinbelow with reference to FIG. 5), said linking means being        connected to one (or more) source(s) of pressurizing gas,    -   one (or more) control connection terminal(s) 22 leading to the        outside of the cartridge 2, and intended to be connected to the        connecting means of the docking station 6,    -   a storage compartment 24 forming a housing for a preserving        fluid (which can be contained in a medical pouch type        container),    -   a recovery reservoir 25 intended to collect user fluids from the        preservation chambers 1,    -   a switching system 26 including one (or more) deformable        valve(s) for controlling the flow rate of the preserving fluid        inside the preservation chambers 1, the pressurization of the        preservation chambers, the circulation of the preserving fluid,        etc.    -   circulation channels (for preserving fluid or gas) 23 extending        inside the cartridge 2 between:        -   the input connection terminal(s) 21 and the storage            compartment 24,        -   the storage compartment 24 and the preservation chambers 1,        -   the control connection terminal(s) 22 and the switching            system 26, and between        -   the preservation chambers 1 and the recovery reservoir 25    -   these channels 23 are advantageously etched in the body of the        cartridge itself in order to avoid the problems associated with        conventional wiring (such as connections, joints, lengths of        tubing, porosity of tubing, especially gas tubing, etc.).

Advantageously, each cartridge can include a radio-frequencyidentification (RFID) tag to ensure the traceability of the cornealsample during its storage.

Each cartridge may further include an inflation balloon, with manualactuation of the inflation balloon increasing the pressure in thestorage compartment 24 and then in the preservation chambers when thecartridge 2 is disconnected from the docking station 6.

1.3. Docking Station

The fact that the device integrates the preservation chambers 1 and itsperipherals in the form of a cartridge 2 facilitates handling andstorage, for example in a docking station that allows the preservationchambers to be maintained at a desired temperature, at a controllablepressure and in a controlled atmosphere (percentages of N₂, O₂, CO₂ inparticular). This integration also improves the sterility of theinterior of the medical device, in particular by separating the circuitsof gas and preserving fluid(s) and connecting them by terminals (withouttubing).

As a guide, an example docking station is shown in FIG. 5. The dockingstation 6 contains temperature control means to maintain its interiorvolume at a set temperature.

This docking station 6 is, for example, a commercially availablepreservation oven. The inner volume of the docking station 6 consists ofa support structure with racks 7 each for receiving one cartridge 2.

Each rack 7 has linking means intended to be connected to the input andcontrol terminals 21, 22 of its associated cartridge 2 to allow the gassupply of the latter. Insertion of the cartridge into the rack 7 allowsthe connection means to be connected to the input terminals. Each rack 7may also include means for checking the presence of the cartridge and/ormeans for reading/writing the RFID tag.

The docking station 6 also contains an injection device 43 such as adiaphragm pump or other system for producing compressed air or gas tosupply each cartridge 2.

The docking station includes a pressure regulation control means, aswell as a pneumatic switching sequential control means of the switchingsystem 26. These monitoring and control means are common to all thecartridges 2 and are sequentially assigned to each of the cartridges 2via the connecting means contained in each of the racks into which thecartridges are inserted. This is in order to advantageously mutualizethe pressure regulation and the flow of preserving fluid within each ofthe cartridges 2 present in the docking station 6.

The docking station 6 can be connected (via a wired or wireless link) toa remote control unit such as a personal computer, or a touch tablet, orany other control unit known to the skilled person.

When inserted into the docking station 6, the cartridge 2 is inlong-term storage mode, with regulated pressure and flow. When thecartridge 2 is removed from the docking station 6, the fluid flow isstopped, and the integrated switching system 26 advantageously allowsthe preserving fluid to be pressurized in its internal circuitsindependently. This, together with the consequent reduction in weightand volume, makes the cartridge extremely mobile, allowing it to bemoved from one point to another.

Different elements of the medical device according to the invention willnow be described in more detail.

2. Preservation Chambers

2.1. Corneal Tissue Locking Means

The device comprises means 14 for locking the corneal tissue 3 inposition so that the epithelial side of the corneal tissue 3 extendsopposite the lid 13.

In the embodiments illustrated in FIGS. 9 and 10, the locking meansdefine, together with the corneal tissue 3, the preservation chambersknown respectively as the “endothelial chamber” 4 and the “epithelialchamber” 5.

Specifically, the locking means include:

-   -   a base 141 on which the base 11 is fixed, and intended to        receive the corneal tissue 3,    -   a flexible retaining ring 142 to hold the corneal tissue 3 in        position on the base 141.

The endothelial chamber 4 and the epithelial chamber 5 may each have atleast three ports:

-   -   an inlet port for the injection of preserving fluid,    -   an outlet for the discharge of the preserving fluid, and    -   a technical port for taking a fluid sample (for example for        analysis) or injecting additional substances into the chamber.

The inlet and outlet ports of the two chambers 4, 5 allow a preservingfluid to be circulated and renewed to optimize the preservation ofcorneal tissue.

Advantageously, the composition of the preserving fluid injected intothe epithelial chamber 5 may be different from the composition of thepreserving fluid injected into the endothelial chamber 4.

2.1.1. Base

The base 141 is the cartridge base. It has a central opening whose upperedge 143 (opposite base 11) is intended to receive corneal tissue. Thediameter of the central opening is preferably approximately equal to thediameter of a cornea (typically between 9 and 13 millimeters indiameter).

The surface of the upper edge 143 of the base 141 (i.e. opposite thebase 11) may be curved to conform to the curvature of the corneal tissue3. In particular, the surface of the upper edge 143 may have a truncatedcone shape, or even a toric shape.

The corneal tissue 3 is intended to be placed on the base 141 so thatthe peripheral scleral ciliary zone of the corneal tissue 3 comes intocontact with the upper edge 143.

The base 141 also includes (at least) one inlet port and (at least) oneoutlet port. The inlet and outlet ports allow the preserving fluid 41 toflow into the endothelial chamber 4, the walls of which are defined by:

-   -   the base 11 of the device,    -   the base 141,    -   the retaining ring 142, and    -   the corneal tissue 3.

2.1.2. Retaining Ring

The retaining ring 142 extends perpendicularly inwards from the sidewall 12.

The hole in the retaining ring 142 can be elliptical or circular. In thecase of a circular hole, the inner diameter of retaining ring 142 ispreferably approximately equal to the diameter of a cornea (typicallybetween 9 and 13 millimeters in diameter) and approximately identical tothe central opening of the base. Thus, the sclera of the corneal tissue3 is intended to come into contact with the inner edge 144 of theretaining ring 142.

The retaining ring is advantageously made of a flexible material so thatit can be bent by elastic deformation to conform to the profile of theupper edge 143. This also allows the retaining ring 142 to absorb anyirregularities in the scleral ciliary zone by squeezing to a greater orlesser extent to ensure calibrated force support and sealing in thecontact area between the corneal specimen 3 and the retaining ring 142.

The retaining ring 142 can be attached to the side wall 12 or can bedetachably mounted on side wall 12. For example, in the embodimentillustrated in FIGS. 9 and 10, the inner side of the side wall 12 has aninwardly extending annular border 121. This annular border 121 isintended to press the retaining ring 142 against the base 141 when sidewall 12 is assembled on the base 11 of the device.

Of course, the annular border 121 can be replaced by a plurality ofstuds arranged on the inside of the side wall 12 and extending radiallyinwards therefrom.

2.1.3. Principle of Operation

The principle of operation of the locking means 14 is as follows.

The corneal tissue 3 is placed on the base 141 so that the endothelialside of the corneal tissue 3 lies opposite the base 11. The peripheralscleral ciliary zone of the corneal tissue 3 comes into contact with theupper edge 143 of the base 141.

The retaining ring 142 is placed on the corneal tissue 3 The inner edge144 comes into contact with the peripheral scleral ciliary zone of thecorneal tissue 3.

The side wall 12 of the device is assembled on the base 11.Specifically, the side wall 12 is moved translationally between theclipping means 111. The shape-reversing spring tabs move out of theiroriginal position when the peripheral flange 122 passes over the hookinglips.

Approaching the base 11, the annular border 121 of the side wall 12tends to press the retaining ring 142 against the base 141. Thetranslational movement of the side wall 12 induces a translationalmovement of the retaining ring 142 towards the base 141 so as to lockthe corneal tissue 3 in position.

The fact that the movement of the retaining ring is rectilinear (i.e.translation of the retaining ring 142 towards the base 141) rather thanhelical (for example when the retaining ring is screwed in) limits therisk of twisting the corneal tissue 3 when it is locked in position.This improves the viability of the corneal tissue thus preserved.Indeed, a twisting of the corneal tissue induces the appearance of foldsin the corneal tissue, these folds causing an accelerated degradation ofthe cells and corneal tissue 3.

When the edge reaches a position in which the peripheral flange 122extends under the hooking lips, the elastic tabs return to theirrespective initial positions so that the hooking lips press the sidewall against the base 11 by applying a pressing force to the peripheralflange 122.

The scleral ciliary zone is compressed between the upper edge 143 of thebase 141 and the inner edge 144 of the retaining ring 142 to hold thecorneal tissue 3 in position in the preservation chambers. The use ofclipping means for assembling the side wall 12 against the base 11ensures that a constant compression force of the scleral ciliary zone isapplied from one medical device to another.

This makes the operation of inserting corneal tissue into the devicerepeatable and easily performed by an operator inexperienced in the useof the device.

The reader will have understood that the above operating principle hasbeen presented with reference to a medical device in which the retainingring 142 is not attached to the side wall 12. It is quite obvious to theskilled person that the steps of placing the retaining ring 142 and theside wall 12 are carried out simultaneously in the case of a medicaldevice in which the retaining ring 142 is attached to the side wall 12.

2.2. Preservative Fluid Supply

Once the corneal tissue has been installed and the preserving fluidcirculation has been started, the corneal tissue can be preserved forseveral weeks prior to its use for corneal transplantation or ex vivoexperimentation.

To increase the storage life of the corneal specimen, a preserving fluidis used.

The management of the supply of preserving fluid to the device isensured by the following set of elements:

-   -   At the cartridge 2:        -   the inlet connection terminal(s) 21 and control terminal(s)            22 intended for connection to one (or more) source(s) of            pressurizing gas,        -   the storage compartment 24 forming a housing for a            preserving fluid: the preserving fluid can be contained            directly in the compartment 24 or be contained in a            container (for example of the medical pouch type) arranged            in the compartment 24,        -   the recovery reservoir 25 intended to collect the user            fluids from the preservation chambers 1,        -   the switching system 26 for controlling the circulation of            the preserving fluid,        -   The circulation channels 23 extending into the cartridge 2,    -   At the docking station 6:        -   the linking means for connection to the input and control            terminals,        -   an injection device 43 using compressed gas to distribute            the fluid 41 and control the switching system 26.

This set of elements allows the circulation and renewal of thepreserving fluid in the endothelial chamber 4 and/or in the epithelialchamber 5. This set of elements also allows the pressure inside theendothelial and epithelial chambers 4, 5 to be varied so as to have acontinuous overpressure in the endothelial chamber 4. This overpressuremay correspond to the pressure physiologically encountered by the corneaon the endothelial side, or it may correspond to any other pressurechosen by the user.

Advantageously, if the compartment 24 of the cartridge 2 comprises twodistinct preserving fluids (for example contained in separatecompartments of compartment 24 or in medical pouch-type containershoused in the compartment 24) each associated with a respective chamber,then the composition of the preserving fluid circulating in theendothelial chamber 4 may be different from the composition of thepreserving fluid circulating in the epithelial chamber 5 (for example amixture of preserving fluid+gas of controlled composition N₂O₂CO₂). Thismakes it possible to have a preservation medium adapted to each celltype (endothelial and epithelial).

The injection device 43 allows the injection of pressurized gas into thestorage compartment 24 and the switching system 26. The injection device43 can be contained in the docking station 6 and connected to thecartridge 2 via the connection terminals 21, 22 of the cartridge 2. Theinjection device 43 is, for example, a gas compressor, or compressed gascartridge, or a connection to a compressed air network, making itpossible to generate two distinct pressures: a regulated pressureintended for pressurizing the endothelial chamber via a switchingelement 432 (such as a valve), and an operating pressure intended forcontrolling the fluid switching elements 26 via the connections 22.

The use of a pressurized gas injection device 43 (instead of the rollerpump described in WO 2014/140434) separate from the cartridge 2 has manyadvantages.

In particular, it makes it possible to:

-   -   reduce the size and weight of the cartridge 2 integrating the        preservation chambers,    -   increase the service life of the cartridge 2 (by avoiding of the        hose wear problem linked to the use of a peristaltic pump),    -   reduce the heat generated by the pump (the motor of a        peristaltic pump emits more calories than a compressed gas        injection device),    -   reduce “jerks” in the regulation of preserving fluid flow and        pressure,    -   regulate more precisely the pressure and flow rate in the        chamber(s),    -   improve the energy efficiency of pressurization-circulation,    -   facilitate the realization of an independent fluidic circuit in        the epithelial chamber, in order to expose it to a preserving        fluid different from the endothelial chamber,    -   facilitate intermittent exposure of the corneal specimen 3 to a        gas flow (such as air or an atmosphere controlled by oxygen        and/or carbon dioxide enrichment) to improve the quality of the        corneal tissue and/or facilitate its imaging (possibility of        filling the epithelial chamber with gas (for example air) which        allows the use of instruments for optical measurement of the        graft (pachymetry or detection of optical aberrations due to        refractive surgery of the donor, as an example by optical        coherence tomography, or specular microscopy),    -   limit the risk of contamination by the external environment,    -   facilitate the transport of the device (from the sampling site        to the corneal bank and from the bank to the operating theatre)        by integrating all the elements necessary for the preservation        of corneal tissue in the device.

Pressurized gas is used to propel the preserving fluid 41 into thepreservation chambers.

2.2.1. “with Contact” Type Fluid Supply

FIG. 6 shows an embodiment in which the preserving fluid 41 is storeddirectly in the storage compartment 24 for a “contact type” fluidsupply.

In this case the compressed gas from the injection device is introduceddirectly into the compartment 24 to propel the preserving fluid 41 tothe endothelial chamber 4 (gas and fluid mix in this configuration). Theadvantage of this solution is that it allows exchanges between the gasand the preserving fluid (for example enrichment with oxygen and/orcarbon dioxide).

In the embodiment illustrated in FIG. 6, the cartridge 2 comprises aswitching element 432 and a filter 433 between the input terminals 21and the control terminals 22 on the one hand, and the storagecompartment 24 on the other hand.

In this embodiment, the operating principle is as follows. The injectiondevice 43 provides:

-   -   a compressed propellant gas regulated in pressure via the inlet        terminal 21, this propellant gas being intended to be injected        into the storage compartment 24, and    -   a compressed control gas via the control terminal 22, which is        used to control the opening and closing of the switching element        432,

The switching element 432 controls the injection of the propellant gasinto the storage compartment 24. Specifically, a compressed control gas(forming a pneumatic control) is applied to the control terminal 22 a toallow the pressurized propellant gas injected via the inlet terminal 21to propagate to the storage compartment 24.

The filter 433 sterilizes the compressed propellant gas from theinjection device 43 prior to its introduction into the compartment 24.The propellant gas injected into the storage compartment pushes thepreserving fluid 41 to the endothelial chamber 4. The medium initiallycontained in the endothelial chamber 4 (for example air when the deviceis closed), is expelled towards the epithelial chamber 5.

2.2.2. Non-Contact Type Fluid Supply

With reference to FIG. 7, an embodiment has been illustrated in whichthe preserving fluid 41 is contained in a container 42 housed in thestorage compartment 24 for a “non-contact” type fluid supply. Thecontainer 42 may consist of a medical pouch comprising two flexible orsoft sheets superimposed and welded at their periphery.

An inflatable balloon to receive the propellant gas is also housed inthe storage compartment 24. This inflatable balloon allows pressure tobe exerted on the outer faces of the walls of the container 42 when itexpands to propel the preserving fluid 41 to the endothelial chamber 4(gas and fluid do not mix in this configuration).

In the embodiment illustrated in FIG. 7, the cartridge 2 has a switchingelement 432 between the terminals 21,22 and the storage compartment 24.

In this embodiment, the operating principle is as follows. The injectiondevice 43 supplies the compressed gases (propellant and control) to theinput and control terminals 22.

The switching element 432—controlled by the pressure sensor—controls theinjection of propellant gas into the storage compartment 24.Specifically, a control compressed gas (forming a pneumatic control) isapplied to the control terminal 22 a to allow the pressurized propellantgas injected via the inlet terminal 21 to propagate to the storagecompartment 24.

The compressed propellant gas is introduced into the inflatable balloon,which tends to press against the walls of container 42 as it expands.

This pressure exerted by the inflatable balloon on the container 42induces the ejection of preserving fluid 41 to the endothelial chamber4.

2.2.3. Switching System

The injection device 43 also supplies control compressed gas to theswitching system 26 via the control terminals 22 b, 22 c, 22 d. Thiscontrol gas is used to control the switching system 26.

FIG. 8 shows an example of a switching system 26 to control the flow andpressure of the preserving fluid within the endothelial chamber 4 andepithelial chamber 5.

The switching system 26 consists of valves V1, V2, V3 that arepneumatically operated (by means of control gas injected into thecontrol terminals 22 b, 22 c, 22 d).

These valves V1, V2, V3 can consist of elastomer valves which aredeformable under the effect of pneumatic pressure. These valves V1, V2,V3 have the particularity of being closed in the absence of pilotpressure. This allows the cartridge 2 to remain under pressure when itis removed from its rack 7.

The valves V1, V2, V3 are operated in a sequence performed in fivesteps.

In a first (so-called initial) step, the three valves V1, V2, V3 areclosed at rest and no liquid can flow through the switching system 26.

In a second step, the injection device 43 emits a control gas into thecontrol terminals 22 b, 22C. The first and second valves V1, V2 openunder the action of the control gas. This allows the preservation mediumto enter the second valve V2 via the first valve V1.

In a third step, the injection device 43 stops the emission of controlgas in the control terminal 22 b. The first valve V1 closes, thustrapping a quantity of preserving fluid in the dead volume of the secondvalve V2.

In a fourth step, the injection device 43 emits a control gas into thecontrol terminal 22 d. The third valve V3 opens to release the fluidcontained in the second valve V2.

In a fifth step, the injection device 43 stops the emission of controlgas in the control terminal 22 c. The second valve V2 closes byexpelling the fluid contained in its dead volume to the third valve V3.

The return to the initial step results in the closing of the third valveV3 which in turn expels the fluid contained in its dead volume towardsthe epithelial chamber 5.

A complete cycle displaces a volume of fluid equivalent to the deadvolume of one valve, and in particular the dead volume of the secondvalve V2. It is therefore the dead volume of the second valve V2, andthe repetition frequency of the sequence that will determine the flow offluid in the cartridge 2.

2.3. Lid

As described above, the device comprises a lid that can be sealinglyengaged in the side wall 12 to delimit the epithelial chamber.

Different types of lids can be used, including an applanation lid 13 ora trepanation lid 15. Specifically, if the applanation lid is mounted onthe side wall, it can be replaced by a trepanation lid, for example forcutting corneal tissue (and vice versa). Therefore, the medical devicemay include a number of different lids that can be mounted on the sidewall 12 depending on the needs of the practitioner.

Different types of lids will now be described in more detail.

2.3.1. Applanation Lid

With reference to FIGS. 9 to 12, an example of an applanation lid 13according to the invention is illustrated. The applanation lid 13 allowsthe corneal tissue 3 to be flattened for imaging or processing in aclosed environment (i.e. without exposing the corneal tissue 3 to theexternal environment) so as to avoid any risk of contamination.

The applanation lid 13 consists of a translationally movable window 131and a support 132 for connecting the window 131 to the side wall 12 ofthe device.

2.3.1.1. Window

The window 131 is made of a material that is transparent to radiation(light and electromagnetic) or ultrasound.

This allows a user to observe (for example using a specular reflectionmicroscope or an OCT or ultrasound device) and/or treat (for exampleusing a laser) the corneal tissue 3 from outside the device withoutopening it (commonly referred to as a “closed vessel”).

The window 131 can be flat or curved. It has an annular bead on itsperiphery. The annular bead is intended to cooperate with an annulargroove in the support 132 to fix the window 131 tightly to the support132.

2.3.1.2. Support

The support 132 is detachably attached to the side wall 12 of thedevice.

The support 132 allows the window 131 to be held in line with thecorneal tissue 3. Advantageously, the support 132 includes means fortranslatory movement of the window 131 in relation to the side wall 12of the device.

Specifically, the support 132 includes means to move the window 131translationally between:

-   -   a resting position in which the window 131 is distant from the        corneal tissue 3 (see FIGS. 9 and 11),    -   an active position in which the window 131 is in contact with        the corneal tissue 3 to flatten it (see FIGS. 10 and 12).

To move from the rest position to the active position, the user applies(with a microscope or laser or other device) a force in the direction ofthe corneal tissue 3, perpendicular to the plane containing the window131 to move the window 131 to the base 11 of the device.

The fact that the window 131 is movable translationally (rather thanrotation as proposed in WO 2014/140434) limits the risk of the cornealtissue 3 twisting when the window 131 comes into contact with it toflatten it, as this twisting can damage the corneal tissue 3 asmentioned above.

Advantageously, the support 132 is made of an elastically deformablesoft material. This guarantees the tightness of the lid 13 and thusimproves the sterility of the device.

The support 132 may include a clearance area to receive a portion of thegas and/or preserving fluid contained in the epithelial chamber 5 whenthe window 131 is in the active position. This limits pressurevariations in the endothelial and epithelial chambers 4, 5 when thewindow 131 is moved from the rest position to the active position.

In the embodiment illustrated in FIGS. 9 to 12, the support 132 consistsof an outer sleeve and the means of translational movement consists ofan annular bellows, the sleeve and the bellows being made in one piece.

The sleeve is intended to be pressed onto the inside of the side wall 12(or alternatively clipped onto an external groove of the side wall 12 bymeans of anchoring means—such as fastening hooks—mounted on the outerring).

The annular bellows extends radially inward from the outer sleeve. Thefree edge of the bellows includes the annular groove intended tocooperate with the annular bead of the window 131 to secure the support132 and the window 131 together. Of course, an adhesive—such asbiocompatible glue—or any other means known to the skilled person can beused to ensure that the window 131 is tightly fixed to the support 132.

The annular bellows may comprise one (or more) pleat(s) (successively).The pleat(s) (generally concavely rounded) allows compression andextension of the bellows as well as flexion on either side of itsresting position.

Preferably the annular bellows is shape-reversing, so that when no forceis applied to the window 131, it returns to its rest position. Thus, assoon as imaging or treatment of the corneal tissue 3 is completed, thewindow 131 automatically returns to the rest position without the userhaving to perform any action. This prevents the corneal tissue 3 frombeing stored for several weeks in a flattened state, which wouldpartially damage it.

2.3.1.3. Principle of Operation

The operating principle of the applanation lid 13 is as follows.

When the user wishes to image the corneal tissue 3, for example to checkthe cell and tissue quality of the corneal tissue, she positions amicroscope head opposite the window 131 and moves it to the base 11 ofthe device.

This induces the translational movement of the window 131 towards thebase 11 of the device: the pleat(s) of the bellows extend(s).

The displacement of the window 131 towards the corneal tissue induces adecrease in the volume of the epithelial chamber. The pleat(s) of thebellows (which constitutes the zone of release) deforms to receive someof the gas or fluid contained in the epithelial chamber 5. This limitspressure variations in the epithelial chamber 5.

The window 131 comes into contact with the corneal tissue 3, which tendsto flatten it when the window 131 is placed against the corneal tissue3. The window 131 continues to move until the user stops moving themicroscope to the base 11 and/or the window comes into contact with theinner edge 144 of the retaining ring 14.

Thus, the applanation lid 13 allows a controlled deformation of thecorneal tissue 3 by contact of the window 131 of the lid with theepithelial face of the corneal tissue 3, while keeping the device tight(closed vessel excluding any risk of contamination).

This applanation lid 13 makes it possible to:

-   -   dampen possible pressure variations (by deformation of the        bellows pleat(s))    -   improve the quality of imaging        -   the optical contact of the imaging device with the window            and the corneal tissue eliminates interfaces with the            preserving fluid or air in the epithelial chamber, thus            improving the imaging obtained for example by specular            microscopy, OCT, ultrasound biometry, confocal microscopy or            any other technique known to the skilled person,        -   by flattening the corneal tissue, it is possible to define a            reference surface (flat or curved), and to improve the            imaging possibilities (wider field, suppression of the            natural curvature of the cornea),    -   make a laser incision in the cornea in a closed vessel, whether        parallel to the flat surface (anterior lamellar grafts of        circular or free form (corneal patch) or endothelial grafts)        and/or perpendicular to the surface (transfixation or lamellar        grafts),    -   reduce the risk of trauma to the corneal tissue (no manipulation        of the graft), and to guarantee its sterility by keeping it in a        closed vessel,

2.3.2. Trepanation Lid

With reference to FIGS. 13 and 14, a second type of lid has beenillustrated, namely a trepanation lid 15.

The trepanation lid 15 allows a circular incision to be made in thecorneal tissue 3. Specifically, the trepanation lid allows a transfixingor non-transfixing (controlled depth) cut to be made in the cornealtissue for transfixing or lamellar grafts.

The trepanation lid 15 includes:

-   -   an outer casing 151 having an axis A-A′, and having a foot part        for its application to the side wall of the device,    -   an inner blade holder 152 movable within the casing 151, and        coaxial to said holder 151,    -   a cylindrical blade 153 also coaxial to the casing 151.

The outer casing 151 has the general shape of a disc. It comprisesradially outwardly extending fastening hooks 154 at its periphery. Eachfastening hook 154 is intended to cooperate with an annular rib 123 onthe outside of the side wall 12 to enable the fastening of thetrepanation lid 15 to the side wall 12. The central part of the outercasing 151 comprises a through passage including a thread with a knownpitch to accurately quantify the penetration of the blade.

The blade holder 152 is intended to be positioned in the through-passageof the outer casing 151. It consists of:

-   -   a distal end including gripping means to enable a user to        manipulate the blade holder 152, and    -   a proximal end carrying the cylindrical blade 153.

The outer face of the blade holder 152 has, between its proximal anddistal ends, a thread complementary to the thread of the outer casing151.

The operating principle of the trepanation lid 15 is as follows. Oncethe trepanation lid 15 is fixed on the side wall 12 of the device, theuser screws the blade holder 152 on the outer casing 151 using thegripping means. This causes the cylindrical blade 153 to move (veryslowly) towards the corneal tissue 3 in a helical movement. The cuttingblade consisting of the lower edge of the cylindrical blade 153penetrates the corneal tissue 3 and allows a circular cut to be madethrough the epithelial surface, thus minimizing endothelial lesions andwith vertical edges.

Advantageously, pressure can be maintained in the endothelial chamber 4during the entire corneal tissue 3 trepanation operation.

CONCLUSIONS

The invention described above improves the operation of the bioreactoraccording to WO 2014/140434, the quality of corneal tissue as well asits imaging, and extends its applications to new functions, such ascorneal cutting in a closed vessel by laser, corneal trepanation etc.

-   a. The device described above increases the storage life of corneal    tissue. It also improves the quality of the corneal tissue stored.    -   In particular, the arrangement of the locking means, and in        particular the translational movement of the retaining ring 142        in relation to the base 141, prevents the corneal tissue 3 from        twisting and thus the appearance of folds in it.    -   In addition, the presence of clipping means 111 for the assembly        of the side wall 12 on the base 11 ensures that a constant        compressive force is applied to the corneal tissue. This makes        the corneal tissue placement operation repeatable from one        medical device to another.-   b. The device described above also improves the imaging quality of    the corneal tissue 3.    -   In particular, the fact that the applanation lid 13 includes        means for translational movement of the window 131 limits the        risk of the corneal tissue 3 twisting during flattening, as this        twisting can degrade the imaging quality of the corneal tissue        3.-   c. Finally, the device described above makes it easier to manipulate    the corneal tissue 3, especially with regard to its removal from the    device and/or cutting, for example during corneal graft surgery.

In reference to the extraction of the corneal tissue 3, the presence ofa zone of weakness on the elastic tabs makes them breakable under theaction of a force of intensity greater than a rupture threshold of thezone of weakness. This facilitates the disassembly of the side wall 12in order to free the corneal tissue 3 during a graft surgery procedure.μ

With reference to cutting of the corneal tissue 3, the fact that atrepanation lid 15 is adaptable on the device (thanks to the fixationhooks and the annular rib) will allow the user to perform an epithelialtrepanation which has many advantages compared to a punch trepanation(rapid vertical compression cutting of the punch type which makesnon-vertical edges and damages the endothelial cells at the cuttingedge) by endothelial way. The device's endothelial pressure regulationsystem remains fully functional and allows the cornea to maintain itspressurization (thus its physiological shape) during the trepanation.This epithelial trepanation lid makes it possible to:

-   -   carry out a perfectly vertical, total or partial cutting    -   minimize endothelial damage in the case of transfixing cutting.

The reader will have understood that many changes can be made to themedical device described above without materially altering the newteachings and benefits described here. Therefore, all such changes areintended to be incorporated within the scope of the attached claims.

The invention claimed is:
 1. A medical device for preserving previouslyremoved corneal tissue, the device comprising an at least partiallytransparent base, at least one side wall, receiver for receiving andlocking the corneal tissue, and an applanation lid for covering anopening opposite the base, the applanation lid including a transparentwindow, wherein the applanation lid further includes a support betweenthe window and the side wall, the support having a translator fortranslating the window relative to the side wall of the device.
 2. Thedevice as claimed in claim 1, wherein the support is made of anelastically deformable soft material.
 3. The device as claimed in claim1, which is configured such that, in use, the receiver defines with thebase, the corneal tissue, the side wall and the lid an endothelialchamber and an epithelial chamber, the endothelial and epithelialchambers including inlet and outlet orifices for the circulation of agas and/or a preserving fluid, the support comprising a clearance zonefor receiving part of the gas and/or the preserving fluid contained inthe epithelial chamber when the window is translated towards the base.4. The device as claimed in claim 1, wherein the translator comprises anannular bellows having at least one pleat.
 5. The device as claimed inclaim 4, wherein the annular bellows is made of a shape-reversingmaterial.
 6. The device as claimed in claim 1, wherein the side wallcomprises an annular rib.
 7. The device as claimed in claim 1, whichfurther comprises a trepanation lid including a circular outer casing, ablade holder, and a cylindrical blade, the applanation lid beingreplaceable with the trepanation lid to cover an opening opposite thebase, for example to perform a cutting of corneal tissue.
 8. The deviceas claimed in claim 7, wherein the side wall comprises an annular rib,wherein the outer casing of the trepanation lid has at least twofastening hooks at its periphery, the fastening hooks extending radiallyand being intended to cooperate with the rib provided in the outer faceof the side wall.
 9. The device as claimed in claim 1, wherein the sidewall comprises a peripheral flange and the base comprises a clipper,said clipper consisting of at least two elastic tabs intended tocooperate with the peripheral flange.
 10. The device as claimed in claim9, wherein the clipper comprise at least three elastic tabs uniformlydistributed around the side wall.